Rhodococcus Equi and Arcanobacterium Haemolyticum: Two “Coryneform” Bacteria Increasingly Recognized As Agents of Human Infection

Synopses Rhodococcus equi and Arcanobacterium haemolyticum: Two “Coryneform” Bacteria Increasingly Recognized as Agents of Human Infection Regina Linder Hunter College, New York, New York, USA Rhodococcus equi and Arcanobacterium haemolyticum, formerly classified in the genus Corynebacterium, are members of the loosely defined taxon “coryneform” bacteria. Although they are the etiologic agents of distinct human infections, both organisms are frequently overlooked, which results in missed or delayed diagnoses. R. equi, long known as an important pathogen of immature horses, has become in the past three decades an opportunistic pathogen of severely immunosuppressed humans. Most cases are secondary to HIV infection. When specifically sought in throat swab cultures, A. haemolyticum is found responsible for 0.5% to 2.5% of bacterial pharyngitis, especially among adolescents. These two microorganisms represent a spectrum of disease in humans: from a mild, common illness to a rare life-threatening infection. Each organism elaborates lipid hydrolyzing enzymes (cholesterol oxidase by R. equi and sphingomyelinase D by A. haemolyticum) that are toxic to animals and humans and damaging to mammalian cell membranes. The participation of the cytotoxins in pathogenicity is discussed. Greater awareness of the properties of these two bacteria may promote faster, more accurate diagnoses and better clinical management. A variety of factors contribute to the under- human pathogens, rigorous biochemical and reporting of human infections caused by bacteria molecular tools have increasingly been applied to in the genus Corynebacterium and closely related isolates. The resulting improved epidemiology genera. The group, often referred to as “coryne- and taxonomy have led, for example, to the defi- form,” comprises taxonomically diverse gram- nition of CDC groups JK and D-2 in the genus positive rods resembling Corynebacterium diph- Corynebacterium, now recognized as important theriae and displaying pleomorphism and irregu- opportunistic pathogens (1). Similarly, more accu- lar cellular arrangements (1,2). The group rate characterization of some species caused includes human and animal pathogens, as well as them to be removed from the genus Corynebac- commensal bacteria. The control of diphtheria in terium. Excellent reviews of the pathogenicity industrialized countries and the subsequent and epidemiology of these diverse genera have deemphasis of the genus Corynebacterium have been published (1,2). This article explores two contributed to discounting isolates characteristic pathogenic coryneform bacteria: Rhodococcus equi, of the genus as contaminants. Even reference a rare often fatal human pathogen, in which laboratories report difficulty in the speciation of virtually all human infections occur among com- gram-positive pleomorphic rods that resemble promised hosts; and Arcanobacterium haemo- corynebacteria (1). Because of the emergence of a lyticum, which is responsible for many respiratory number of coryneform bacteria as important infections in healthy people. This article aims to bring about improved recognition of these two easily overlooked pathogens and considers mecha- Address for correspondence: Regina Linder, School of Health Sciences, Hunter College, 425 East 25th St., New York, NY 10010, nisms underlying the diseases, the immune USA; fax: 212-420-9135; e-mail: [email protected]. response of the hosts, and treatment protocols. Vol. 3, No. 2, April–June 1997 145 Emerging Infectious Diseases Synopses Epidemiology and Clinical Presentation with antimicrobial agents than cases in AIDS patients (8). Most often, patients have a slowly R. equi progressive granulomatous pneumonia, with Originally isolated by Magnusson in 1923 lobar infiltrates, frequently developing to cavitating from granulomatous lung infections in young lesions visible on chest x-ray. Other sites of horses (3), Corynebacterium (now Rhodococcus infection include abscesses of the central nervous equi) remains an important pathogen of foals. system, pelvis, and subcutaneous tissue, and Much of the considerable body of knowledge about lymphadenitis (7,8-10). Cases of lung infection R. equi, including its pathogenicity and immune caused by inhalation and cutaneous lesions caused response to infection, derives from veterinary by wound contamination have been documented; studies and has been recently updated (4). the latter are almost the only R. equi infections R. equi is readily found in soil, especially reported in healthy persons, frequently children where domesticated livestock graze (5). The stool (11). Delays in accurate diagnosis of R. equi are of horses and other animals is the source of soil still common (2,7), despite increased awareness contamination. Infection in humans derives from of this organism as an opportunistic pathogen in environmental exposure (2,5), and the organism humans. Factors for delayed diagnosis include may be ubiquitous in soil (6). While early cases the insidious onset of disease, clinical resemblance occurred mostly in persons with a history of of the infection to mycobacterial, fungal, and contact with horses, only 20% to 30% of recent actinomycotic infections, and the relatively non- cases can be traced to such contact (7). A review of descript bacteriologic profile of R. equi. Morphology, cases in the three decades since the first reported partial acid fastness, and a distinctive histo- human infection in 1967 is presented in Table 1. pathologic profile in bronchial specimens (Figure 1 R. equi is a rare opportunistic pathogen found A and B) contribute to accurate diagnosis. in severely compromised patients, and most com- Numerous polymorphonuclear leukocytes with monly in recent years, in human immunodefi- intracellular pleomorphic gram-positive bacteria, ciency virus (HIV)-infected persons. Early cases, microabscesses, pseudotumors, and malakoplakia most in patients receiving immunosuppressant are noted on tissue (7,11). Malakoplakia is a therapy, were more likely to be successfully treated relatively rare granulomatous inflammation not Table 1. Rhodococcus equi case reports in humans: 1967–1996 Primary site Predisposing condition of infection Years Cases (number) (number) Deaths Referencesa 1967–76 7 Corticosteroid (1) Lung (6) 0 8–10 Cancer/immunosuppressant (3) Lymphatic (1) Renal transplant (2) Noneb (1) 1977–86 15 Corticosteroid (1) Lung (14) 8 8–10,22 Cancer/immunosuppressant (4) Blood (1) Renal transplant (2) HIV (7) Alcoholism (1) 1987–96 93 Cancer/immunosuppressant (8) Lung (72) 34 8–13,22 Renal transplant (3) Lymphatic (2) HIV (67) Blood (8) Otherc (8) (1b) Wound (6) None (7) (4b) Otherd (5) aIn the interest of space, case compilations are cited in lieu of individual case reports. bChild cIncludes intravenous drug use, lab infection, emphysema, kidney disease. dCentral nervous system, gastrointestinal Emerging Infectious Diseases 146 Vol. 3, No. 2, April–June 1997 Synopses A Corynebacterium haemolyticum A. haemolyticum was first described and named by MacClean et al. (14), who isolated it from pharyngeal infections in U.S. soldiers and natives in the South Pacific. Classification of the organism generated controversy until the defini- tion in 1982 of a new genus, Arcanobacterium (secretive bacterium), in which it remains the only species (15). Unlike R. equi infection, where invasive clinical disease underscores the need to detect and identify the causative agent of infection, A. haemolyticum infection is often reported from deliberate screening for the organism of a large number of patients with sore throats. After it was identified B during World War II from patients with pharyngitis (14), it was occasionally reported from Europe, the United States, and in 1981, Sri Lanka (16 cases) (16). Most cases involve pharyngitis and/or tonsillitis, and approximately 50% are exudative. Throat infections are often accompanied by cervi- cal lymphadenopathy (17,18). Diagnosis of cases (distinct from screening studies) often occurs only after recurrent infections, which are thought to be related to incorrect initial diagnosis, resulting in less-than-optimum treatment (19). Infection is most common in 15- to 25-year-old persons, and is Figure 1. A. Bronchial tissue Gram stain showing thought to result from droplet transfer from intrahistiocytic coccobacillary forms of Rhodococcus infected persons (20). Symptoms resemble those equi. Original magnification, x 1,000. B. Open lung of ß-hemolytic streptococci or viral infection. The biopsy showing coalescent microabscesses with spectrum of disease ranges from sore throat to, in numerous histiocytes containing Rhodococcus equi rare cases, a life-threatening membranous pharyn- organisms. PAS stain. Original magnification x 250. gitis resembling diphtheria (18,20). An erythe- Figure provided by Dr. Margie Scott, Vanderbilt matous morbilliform or scarlatinal rash of the University Medical Center. trunk, neck, or extremities is associated with 20% to 25% of cases (19), enhancing the possibility of misdiagnosis as streptococcal infection or penicillin typically associated with histology of lung infec- allergy, because ß-lactam therapy is frequently tion and can be of help in forming a differential initiated without accurate diagnosis. A recent diagnosis (11,12). Firm diagnosis and differen- report des-cribes in detail the dermatologic tiation from similar pathogens require the isola- manifestations of A. haemolyticum infection (20). tion and identification of R. equi from sputum, The

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